Background Atypical antipsychotics may be beneficial in treating the core psychopathology of anorexia nervosa (AN). Methods An 8 week open-label study of quetiapine was conducted in eight severely ill DSM-lVAN patients consecutively admitted to a specialist eating disorders unit. Participants were assessed by EDE-12, MADRS, YBOCS, SAPS-delusions and CDR neuropsychological battery at baseline, 4 weeks and 8 weeks, and by weekly body mass index (BMI), CGI and extrapyramidal scores. Quetiapine doses ranged from 50 mg to 800 mg per day, according to efficacy and tolerability. Results Seven participants completed 4 weeks and five participants completed 8 weeks. All participants had clinically significant levels of specific eating disorders psychopathology, and mild to moderately severe depressive symptomatology. Apart from initial mild sedation, no subjects experienced any significant adverse events. Over 4 weeks there was no significant difference in BMI, but a significant difference in the EDE- 12 restraint score. There were significant differences on BMI and EDE-12 restraint subscale scores over 8 weeks. Conclusions A double-blind placebo controlled study is required to further evaluate the therapeutic utility of quetiapine in severely ill AN patients beyond multidisciplinary specialist intervention. Copyright (c) 2007 John Wiley & Sons, Ltd.